1. Field of the Invention
This invention relates to an improved method of preparing an implantable paste for placement between injured bones or placement in bony voids to induce regeneration, and the compositions produced thereby. Specifically, mineral, ceramic, or processed bone particles, so-called bioactive particles (BP), are coated with a matrix material (MM) capable of forming a viscous gel when reconstituted with water, saline, autologous blood, sera, or other medically acceptable solution. This MM may be a natural or synthetic polymeric material, producing a wettable paste upon exposure to water, saline, or another aqueous solution. In storage, the composition will be granular and dry, but easily wetted during reconstitution. To prepare the composition for administration, the material is reconstituted to a viscous malleable paste by the simple addition of water or other medically acceptable solution without the need for aggressive mixing. The paste may be delivered by syringe or manually deposited yet will be resistant to lavage or to displacement by gravity induced flow.
2. Description of Related Art
Bone pastes, such as REGENAFIL™ or OSTEOFIL™ produced by Regeneration Technologies, Inc., comprise particles of allograft demineralized bone matrix (DBM) and gelatin (U.S. Patent Applications 20020098222, 20020018796, and 20020076429). As taught by Scheicher (U.S. Pat. No. 4,191,747), suspending osteoinductive and/or osteoconductive materials in gelatin solutions provides an implantable composition with temperature dependant flow properties. Above the gel transition temperature, the composition is free flowing while below that temperature, i.e. when at body temperature, it forms a stable mass resistant to deformation and dissolution.
However, there are some drawbacks to such compositions. If provided as a pre-mixed suspension of DBM and hydrated gelatin, the product must be stored frozen to prevent degradation of the osteoinductive capability of the DBM. Prior to use, frozen material must not only be thawed but raised above the gel transition temperature in order to yield a free-flowing paste.
Regeneration Technologies, Inc. produces a version of OSTEOFIL™ that can be stored at room temperature. This version is comprised of a mixture of DBM particles and gelatin particles. The drawback of this paste composition and method of preparation is that heated liquid and/or aggressive mixing is required to produce a uniform and free-flowing suspension (U.S. Patent Applications 20010016703, 20010037091, 20030180262).
It is conventional to store drugs, vaccines, medicaments, and solutions in a sealed vial or other container for later use. Drugs, vaccines, medicaments, and solutions may be stored in a dry or powdered form to increase the shelf life and reduce inventory space. Such dry or powdered materials are typically stored in a conventional sealed vial having a puncturable closure, such as an elastomeric stopper, and reconstituted in liquid form for later use, such as administration to a patient, by adding a diluent or solvent.
Dry materials available for reconstitution may also be stored directly in a syringe. For example, as described in U.S. Pat. No. 6,773,714 (Dunn, 2004), leuprolide acetate, a peptide drug, is lyophilized directly in a syringe prior to use. A biodegradable polymer and solvent solution is filled into another syringe. The two syringes are coupled together and the contents are drawn back and forth between the two syringes until the polymer/solvent solution and the leuprolide acetate are effectively mixed together, forming a flowable composition. The flowable composition is drawn into one syringe and the two syringes then disconnected. A needle is inserted onto the syringe containing the flowable composition and then injected through the needle into the body. Other flowable compositions are described in U.S. Pat. Nos. 5,324,519; 4,938,763; 5,702,716; 5,744,153; and 5,990,194. None of these techniques, though, anticipate the preparation of an easily dispersible bioactive particle composition, prepared from the precipitation of a high molecular-weight polymer onto the bioactive particle, with the described characteristics in the present invention.